摘要
目的研究组蛋白去乙酰化酶抑制剂滴菌素A对胶原诱导性关节炎（CIA）小鼠辅助性T细胞（Th）1和Th17细胞分化的影响，探讨其作用机制。方法将雄性DBA／1小鼠按照随机数字表法分为CIA模型组、滴菌素A组、正常对照组。免疫后第35天处死小鼠，检测小鼠足爪炎症的肿胀程度，病理切片观察炎症变化，四甲基偶氮唑盐（MTF）法检测脾淋巴细胞对胶原的增殖反应，实时荧光定量PCR检测各组小鼠IFN-γ、114、IL-10、IL-17mRNA及T盒21转录因子（T_bet）、与GATA序列结合的锌指结构家族（GATA-3）、叉头框蛋白3（Foxp3）、孤儿素受体＂yt（RORTt）mRNA的变化，双抗体夹心ELISA法检测血清IFN-γ、IL4、IL-10、IL-17的含量。数据采用SPSS10．0软件进行单因素方差分析，两两比较采用SNK检验。结果模型组IFN-1、IL，17mRNA相对表达量（8．27±0．64，5．80±0．23）高于正常对照组（2．97±0．25，0．70±0．26，P均〈0．01）。滴菌素A组关节炎指数（2．83±O．10）和增殖指数（1．28±0．03）低于CIA模型组（3,61±0．25，1．64±0．06，P均〈O．05）；滴菌素A组IFN-γ、IL-17mRNA相对表达量（6．60±0．52，2．50±0．41）低于模型组（8．27±0．64，5．80±0．23，P均〈0．01），而IL-4表达量（2．10±0．17）高于模型组（1．01±0．08，P〈0．01）。结论Thl和Th17在CIA的发生发展中具有重要的作用，滴菌素A可能通过抑制T细胞增殖及影响Th1和Th17细胞分化格局来延缓CIA的进一步发展。
Objective To investigate the effects of trichostatin A （TSA） on Thl and Th17 cells in the mice model of collagen induced arthritis （CIA）. Methods Mice model of rheumatoid arthritis （RA） was induced in DBA/1 mice with type Ⅱ collagen. Paws were scored for histological severity of arthritis. The severity of inflammation of mice joints was evaluated by histological examination. Real time polymerase chain reaction （PCR） was used to determine mRNA of cytokines and transcriptional factors. Serum cytokine production was measured by enzyme linked immunosorbent assay （ELISA）. T cell proliferation was examined by MTI＂ method. One-way ANOVA and Student-Newman-Keuls were conducted in this study. Results The expressions of IFN-~/and IL-17 mRNA of the CIA group were higher than that of the control group （8.27±0.64 vs 2.97±0.25, 5.80±0.23 vs 0.70±0.26, all P〈0.01）, but were inhibited significantly by TSA introduced at the onset of arthritis（6.60±0.52, 2.50±0.41, all P〈0.01 ）. Collagen specific T cell proliferation was significantly suppressed by the introduction of TSA. Increased level of IL-4 was observed in TSA treated group compared to that of CIA group（2.10±0.17 vs 1.01±0.08, P〈0.01 ）. Conclusion Thl and Th17 cells play crucial roles in the lesions of RA. TSA can suppress the progress of CIA by decreasing the percentage of Thl and Th17.
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2014年第1期39-44,I0002,共7页
Chinese Journal of Rheumatology
基金
基金项目：国家自然科学基金（30800998）
关键词
类风湿
关节炎
实验性
干扰素Ⅱ型
白细胞介素类
T淋巴细胞
辅助
诱导
滴菌素A
Arthritis, rheumatoid
Arthritis, experimental
Interferon type II
Interleukins
T-lymphocytes, helper-inducer
Trichostatin A
